It is generally accepted that the suppression of the immune response in man greatly enhances the development of lymphoid leukemias and lymphomas. Under experimental conditions, murine oncornaviruses have been shown to have immunosuppressive functions that appear independent from their malignant (transforming) functions. As yet, however, the question of whether immunosuppression by oncornaviruses occurs under natural conditions in the development of spontaneous leukemia has not been tested. The previous work in our lab has been concentrated in two areas: (a) the natural history and mechanisms of immunosurveillance in feline leukemia, and (b) the mechanisms and significance of immune suppression in experimental murine leukemia. In the current proposal we plan to investigate the nature and role of feline leukemia virus (FeLV)-associated immunosuppression in induced and spontaneous feline leukemia. Our experimental results have already shown that the blood and lymphoid organs of cats in the latent phase of leukemia contain a population of suppressor cells that are capable of inhibiting immunocompetent cells. The methods will involve both B and T cell functions and the phagocytic apparatus. These will include the response to standard B and T cell mitogens, the in vivo and in vitro response to feline enteritis virus, the response of T cells in mixed lymphocyte culture, the homograft rejection reaction, the delayed hypersensitivity skin reaction to cat flea antigen, the immune response to FeLV and FeLV-associated cell membrane antigens, and macrophage phagocytic function tests. The cats studied will include those with spontaneous leukemias, those with FeLV-induced leukemia during both incubation and clinical stages, and most importantly, cats with naturally acquired persistent FeLV viremia that are still healthy but at very high risk for spontaneous leukemia development.